Method and composition for preventing or reducing the symptoms of insulin resistance syndrome

ABSTRACT

A method for preventing and or reducing the symptoms of insulin resistance and a related syndrome in persons comprises identifying persons having or at risk for having such symptoms, and administering to them an effective amount of a composition comprising chromium bound niacin that prevents or reduces the symptoms. Compositions incorporating chromium bound niacin and additional compounds also are disclosed that are particularly effective in preventing or reducing these symptoms.

PRIORITY CLAIM

This application is a continuation of Ser. No. 10/265,093, titled:Method and Composition for Preventing or Reducing the Symptoms ofInsulin Resistance Syndrome, inventors: Debasis Bagchi, Harry G. Preussand Shil C. Kothari, filed Oct. 4, 2002 (IHEAL-01037US1) which claimspriority to U.S. Provisional Patent Application Ser. No. 60/327,896,titled: Method for Preventing or Reducing the Symptoms of InsulinResistance Syndrome, inventors: Debasis Bagchi, Harry G. Preuss and ShilC. Kothari, filed Oct. 5, 2001 (IHEAL-01037US0). These applications areherein incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION

The present invention relates generally to a method and composition forpreventing or reducing the symptoms of insulin resistance syndrome in aperson.

An insulin resistance syndrome that has been identified as “Syndrome X”by previous research is a common metabolic disorder affecting more than75 million Americans to some degree. Insulin resistance is a conditionin which the body becomes resistant to its own insulin. The body of theperson affected compensates by releasing more insulin, elevating bodyinsulin levels. This elevated insulin level leads to increased risk of avariety of symptoms, including diabetes, obesity, and heart disease.

Syndrome X appears to be highly prevalent in the obese. Individualelements of Syndrome X (obesity, hypertension, lipid disturbances, andglucose intolerance) are frequently encountered during a typicalperson's life span, and they tend to be increasingly apparent as peopleage, usually becoming most prevalent after age 35. Theoreticalconsiderations suggest that insulin resistance may be a primary factorthat plays a causative role in the induction of both obesity anddiabetes. Atherogenic risk factors associated with obesity and SyndromeX contribute independently to the development of atheroscleroticdisease, and risk of a cardiovascular event increases sharply with theburden of risk factors associated with obesity.

Animal models of Syndrome X, as observed in rats fed high fat diets,exhibit excess accumulation of muscle triglyceride coincident withdevelopment of insulin resistance. This also seems to occur in humans;several studies demonstrate increased muscle triglyceride content ininsulin resistant states. There is substantial evidence indicating thatexcess muscle and liver lipid accumulation causes or exacerbates insulinresistance in Syndrome X and in Type II diabetes. Development ofstrategies to prevent this, therefore, seem worthwhile.

Avoiding weight gain from adolescence to middle age is known to reducecardiovascular morbidity and mortality. Despite much debate in the pastregarding the influence of obesity on health and the benefits ofmaintaining normal weight, it is clear that changes in weight correlateto changes in several atherogenic risk factors. Recent perspectivestudies indicate a continuous graded influence of body mass index (BMI),the ratio of weight expressed in kilograms divide by the height meterssquared, on the rate of coronary disease development. Increased risk isevident at BMI levels below average, indicating that moderate obesitycan be unhealthy. Central obesity, typically including measurements ofwaist girth or waist to hip ratio, has been shown to be moremetabolically disadvantageous than other forms of obesity and, as aconsequence, it is considered a strong predictor of cardiovasculardisease.

The mechanism whereby obesity and weight gain promote atherogenic riskfactors and, in turn, cardiovascular disease is well established. Excessbody fat has been shown to increase resistance to insulin action andreduce uptake of glucose by peripheral tissues. Abdominal obesity, inparticular, is associated with insulin resistance, hyperinsulinemia, arelative deficiency of lipoprotein lipase, elevated triglycerides,reduced HDL-cholesterol and small dense LDL-particles. Obesity maypromote increased absorption in the renal tubules, expanding bloodvolume and inducing an autonomic imbalance that results in hypertension.In addition, insulin resistance often eventuates into glucoseintolerance and diabetes which in turn accelerates atherogenesis.

Obesity is clearly the most prevalent metabolic disorder in the UnitedStates, and weight control deserves a high priority to curbcardiovascular disease and the associated predisposing conditions, suchas lipidemia, hypertension and glucose intolerance. The benefits ofweight control on the major atherogenic risk factors and the insulinresistance syndrome should provide a strong incentive and rationale forcontrol of obesity. There is no other risk factor that affects thecardiovascular risk profile as strongly. It is well known thatnon-insulin dependent type II diabetes is highly associated withobesity. It has been reported that healthy persons with elevated insulinlevels have increased levels of LDL cholesterol, decreased HDLcholesterol and high blood pressure compared with healthy individualswho have normal insulin levels. Diabetes is associated with high bloodlipids, hypertension and a tendency of blood platelets to clot, whichcan block arteries resulting in heart attack or stroke. Diabetes causesa defect in glucose homeostasis. Weight control is a logical firstapproach to avoid moderate degrees of hypertension, dyslipidemia,glucose tolerance and hyperinsulinemia that constitute Syndrome X.

To overcome glucose tolerance, patients with syndrome X secrete largeamounts of insulin. Treatment of Syndrome X should therefore be aimedat: 1) increasing insulin sensitivity; 2) attenuating day-longhyperinsulinemia; and 3) pharmacologic treatment of the specificmanifestations of syndrome X, if lifestyle interventions such as weightloss are not entirely successful. The two major lifestyle modulators ofinsulin action are body weight and physical fitness; the heavier and themore sedentary a patient is, the greater the degree of insulinresistance and compensatory hyperinsulinemia.

However, even with control of weight, many people can still developSyndrome X. Also, many people find controlling their weight to bedifficult, and they are unsuccessful in their attempts. Therefore,pharmocological treatments are needed to help reduce the effects ofSyndrome X in persons.

Chromium helps insulin metabolize fat, turn protein into muscle andconvert sugar into energy. It is an essential trace element required fornormal protein, fat and carbohydrate metabolism. Chromium levels areknown to decrease with age, and marginal chromium deficiencies appear tobe widespread. Chromium is important for energy production and plays arole in regulating appetite, reducing sugar cravings, and increasinglean body mass.

Chromium bound niacin or niacin bound chromium (also called chromiumnicotinate or chromium polynicotinate) dramatically increases theeffectiveness of chromium in a person ingesting it. Normally, chromiumis poorly absorbed and utilized by the body. However, researchers havefound that the most potent form of chromium in nature is that form boundto the B-vitamin, niacin. Furthermore, previous research discoveries ledto the identification of Glucose Tolerance Factor or “GTF”, abiologically active form of chromium that facilitates normal insulinfunction, which is responsible for normal glucose (blood sugar)metabolism. Researchers have found that a particular oxygen-coordinatedchromium niacin complex is the most potent form of all, being overeighteen times more potent than the next closest form of chromium boundniacin tested.

In 1997, researchers at the University of Texas, Austin, showed that acombination of administration of chromium bound niacin along withexercise in obese women resulted in a significant weight loss in womenand also lowered the increase in insulin levels when the women wereorally fed glucose. In contrast, those taking chromium picolinate, adifferent form of chromium, were found to show significant weight gain.In 1999, researchers at Georgetown University Medical Center showed thatcompared to a placebo, chromium bound niacin caused significant loss ofbody fat and sparing of muscle (lean body mass) in overweightAfrican-American women. Also, tests on the blood chemistries of thewomen revealed no significant adverse effects from the ingestion of 600μg of elemental chromium daily for 2 months. This observationdemonstrated the safety of administration of chromium bound niacin atthe tested levels.

In 1994, researchers at Auburn University showed that supplementationwith 200 μg of chromium bound niacin significantly lowered moderatelevels of cholesterol by an average of 14 percent and improved the ratioof total cholesterol to HDL (“good”) cholesterol by 7 percent in maleathletes. In 1995, researchers at Georgetown University Medical Centershowed that a combination of chromium bound niacin and soluble fiber(i.e., guar) significantly inhibited sugar-induced high blood pressurein rats. In 1997, researchers at Georgetown University Medical Centershowed that chromium bound niacin inhibited sugar-induced high bloodpressure, improved long-term blood sugar status and reduced liver andkidney lipid peroxidation in rats. In 2000, researchers at GeorgetownUniversity Medical Center showed that a combination of chromium boundniacin and grape seed proanthocyanidin extract significantly loweredboth total cholesterol levels and LDL (“bad”) cholesterol levels by 10and 14 percent, respectively, in people with elevated blood cholesterollevels.

Diabetic patients have been found to have lower serum chromium levelsand a higher chromium excretion rate. Treatment with chromium boundniacin has been found to improve glucose tolerance in diabetic patients.Dietary trivalent chromium has been shown to have significant beneficialeffects on the insulin system.

It has been demonstrated that essential hypertension may be due toinsulin perturbations. As high dose chromium supplementation seemsnontoxic, chromium may prove to be a useful means to lower bloodpressure in some essential hypertensives as well as diabetichypertensives. It also has been shown that chromium supplementation mayprove to be the most useful means to prevent or treat type II diabetesmellitus and related cardiovascular disorders. Chromium supplementationamplifies insulin receptor tyrosine kinase activity, which explains therelationship between chromium and its effects in diabetes. Chromiumfurther reduces vascular smooth muscle calcium loads and thus reducesperipheral vascular resistance in insulin-resistant states.

Recently, the U.S. Department of Agriculture (USDA) found that manymiddle-age diabetics could overcome their symptoms by taking a chromiumsupplement. The USDA's findings suggest that very low chromium intakesmay be putting millions of Americans on the road to diabetes (and highblood cholesterol) and that the process could be reversed bysupplementing with chromium. A separate study found that marginalchromium loss in male athletes resulting in impaired insulin functioncan be improved by supplementation with chromium bound niacin.

However, though the above studies demonstrate that administeringchromium bound niacin may serve as a beneficial therapeutic method forreducing or preventing the various symptoms associated with Syndrome X,this has not been entirely effective. Improved methods and compositions,therefore, are necessary to provide for preventing or and reducing thesymptoms of Syndrome X in persons. The present invention fulfills thisneed and provides for further advantages.

SUMMARY OF THE INVENTION

The present invention resides in a method for preventing or reducing thesymptoms of insulin resistance in a person, the method comprising:identifying a person suffering from or at risk for suffering from thesymptoms; and administering a composition comprising an effective amountof chromium bound niacin that, when administered to the person,alleviates, reduces or prevents the symptoms. The method preferablyincorporates administering a composition comprising between about 50 andabout 1,000 μg chromium bound niacin, preferably in two doses per day.

In a preferred aspect of the method, the composition incorporates threecompounds selected from the following group: (−)-hydroxycitric acid,zinc, trans resveratrol, gymnemic acid, selenium, anthocyanidinc,allicin, or saponins.

Preferably, if present, the amount of (−)-hydroxycitric acid in thecomposition is between about 250 and about 2,500 mg, the amount of zincin the composition is between about 5 and about 50 mg, the amount oftrans-resveratrol in the composition is between about 5 and about 50 mg,the amount of gymnemic acid in the composition is between about 50 andabout 200 mg, the amount of selenium in the composition is between about0.025 mg and about 0.1 mg, the amount of anthocyanidins in thecomposition is between about 5 and about 50 mg, the amount of allicin inthe composition is between about 2 and about 8 mg, and the amount ofsaponins in the composition is between about 100 and about 300 mg.

The present invention also resides in a composition comprising chromiumbound niacin and three compounds selected from the group consisting of(−)-hydroxycitric acid, zinc, trans-resveratrol, gymnemic acid,selenium, anthocyanidins, allicin, and saponins. Preferred compositionsinclude amounts of these compounds in the above referenced amounts.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention resides in a method for preventing or reducing thesymptoms of Syndrome X in a person, incorporating a step of identifyinga person having the Syndrome, and then administering an amount ofchromium bound niacin to the person sufficient to prevent or reduce thesymptoms of the Syndrome. The present invention also resides incompositions incorporating chromium bound niacin that, when ingested insufficient quantity by a person, prevent or reduce the symptoms ofSyndrome X in the person.

The method of the present invention involves first identifying a personhaving Syndrome X. A diagnosis of Syndrome X is made based on observingsome or all of the following common symptoms: impaired glucosetolerance, hyperinsulinemia, diabetes, hypertriglyceridemia, elevated LDcholesterol, low HDL cholesterol, hypertension, diabetes, andhypertension. Then, the person is administered an effective amount ofchromium bound niacin, on a daily basis. Preferably, the amount ofchromium bound niacin administered to an adult ranges from about 100 toabout 1000 μg per day, taken in two daily doses. The chromium boundniacin preferably is administered orally in a variety of forms,including capsule, tablet, beverage, food additive, powder, liquid, orfood.

Preferred aspects of the method of the present invention involveadministration of additional compounds along with the chromium boundniacin, including: one or more of the following: (−)-hydroxycitric acid;zinc, preferably from zinc methionine; trans-resveratrol; gynmemic acid;selenium; anthocyanidins, preferably from bilberry, blueberry, or grapeseed extracts; allicin, preferably from garlic; and saponins, preferablyfrom fenugreek. These components work synergistically with the chromiumbound niacin to improve its function in alleviating, preventing orreducing the symptoms of Syndrome X. Particularly preferred compositionsadministered include any three of the components in the followingamounts: 50 to 1000 μg chromium bound niacin; 250 to 2500 mg(−)-hydroxycitric acid; 5 to 50 mg zinc; 1 to 5 mg trans-resveratrol; 50to 200 mg gymnemic acid; 0.025 to 0.1 mg selenium; 5 to 50 mganthocyanidins; 2 to 8 mg allicin; and 100 to 300 mg saponins.

EXAMPLE

Studies were conducted to evaluate the efficacy of a combination ofnatural products, including chromium bound niacin, on lowering highblood pressure, one of the particular symptoms commonly associated withSyndrome X. One half of a group of 100 normotensive rats were fed a dietcontaining the following: chromium nicotinate at a human equivalencydosage of 400 μg of elemental chromium (marketed under the brand nameChromeMate by InterHealth Nutraceuticals of Benicia, Calif.), zincmethionine (marketed under the brand name OptiZinc by InterHealthNutraceuticals), and grape seed extract incorporating proanthocyanidins(marketed under the brand name ActiVin by InterHealth Nutraceuticals).The rats that were placed on diets containing supplemental chromiumnicotinate had significantly lowered blood pressure and lipidperoxidation in their livers and kidneys than rats fed normal diets.Sugar-induced hypertension also was reduced in the rats, along withhepatic and renal lipid peroxidation and glycosylated hemoglobin levels.

Although the invention has been disclosed in detail with reference onlyto the preferred embodiments, those skilled in the art will appreciatethat additional methods and compositions can be made without departingfrom the scope of the invention.

1. A method for reducing a symptom of syndrome X in a person, the methodcomprising: (a) identifying a person suffering from or at risk forsuffering from the symptom; (b) administering a composition comprisingan effective amount of chromium; and one or more other compoundsselected from the group consisting of (−)-hydroxycitric acid, zinc,trans-resveratrol, gymnemic acid, selenium, an anthocyanidin, allicin,and a saponin; and (c) testing for a reduction in said symptom.
 2. Themethod of claim 1, where in step (c) the symptom is selected from thegroup consisting of tendency of blood platelets to clot, elevated bloodpressure, obesity, central obesity, elevated body mass index, insulinresistance, hyperinsulinemia, hypertension, serum glucose, glucosetolerance, glucose intolerance, lipoprotein lipase deficiency, liverlipid peroxidation, kidney lipid peroxidation, dyslipidemia,hyper-lipidemia, lipid accumulation, elevated triglycerides, reducedhigh density lipoprotein (HDL), increased low density lipoprotein (LDL)and the LDL to HDL ratio.
 3. The method of claim 1, wherein step (b)involves administering the composition in two doses per day.
 4. Themethod of claim 1, wherein said chromium is chromium bound to niacin. 5.The method of claim 1, wherein said other compound is (−)-hydroxycitricacid.
 6. The method of claim 1, wherein said other compound is zinc. 7.The method of claim 1, wherein said other compound is trans-resveratrol.8. The method of claim 1, wherein said other compound is gymnemic acid.9. The method of claim 1, wherein said other compound is selenium. 10.The method of claim 1, wherein said other compound is an anthocyanidin.11. The method of claim 1, wherein said other compound is allicin. 12.The method of claim 1, step said other compound is a saponin.
 13. Themethod of claim 4, wherein step (b) involves administering thecomposition comprising an amount between: about 50 μg; and about 1000 μgof chromium bound to niacin.
 14. The method of claim 5, wherein step (b)involves administering the composition comprising an amount between:about 250 mg; and about 3000 mg of (−)-hydroxycitric acid.
 15. Themethod of claim 6, wherein step (b) involves administering thecomposition comprising an amount between: about 5 mg; and about 50 mg ofzinc.
 16. The method of claim 7, wherein step (b) involves administeringthe composition comprising an amount between: about 5 mg; and about 100mg of trans-resveratrol.
 17. The method of claim 8, wherein step (b)involves administering the composition comprising an amount between:about 50 mg; and about 200 mg of gymnemic acid.
 18. The method of claim9, wherein step (b) involves administering the composition comprising anamount between: about 0.025 mg; and about 0.1 mg of selenium.
 19. Themethod of claim 10, step (b) involves administering the compositioncomprising an amount between: about 5 mg; and about 100 mg of ananthocyanidin.
 20. The method of claim 11, wherein step (b) involvesadministering the composition comprising an amount between: about 2 mg;and about 8 mg of allicin.
 21. The method of claim 12, wherein step (b)involves administering the composition comprising an amount between:about 100 mg; and about 300 mg of saponins.
 22. A method for reducingexcess liver and/or muscle lipid accumulation comprising: (a)identifying a person suffering from or at risk for suffering from thesymptoms; (b) administering a composition comprising an effective amountof chromium bound niacin, (−)-hydroxycitric acid, gymnemic acid; and oneor more other compounds selected from the group consisting of zinc,trans-resveratrol, selenium, an anthocyanidin, allicin, and a saponin;and (c) testing for a reduction in liver and/or muscle lipidaccumulation.